Genes and Nutrition最新文献

{"title":"Exploring causal relationships between circulating micronutrients and age-related eye diseases: a Mendelian randomization study.","authors":"Xiang Cao, Zijiao Xu, Boyang Zhang, Zhixin Jiang, Xiaoyong Yuan","doi":"10.1186/s12263-025-00767-8","DOIUrl":"10.1186/s12263-025-00767-8","url":null,"abstract":"<p><strong>Background: </strong>With the global population aging, age-related eye diseases (AREDs) such as senile cataract (SC), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are becoming increasingly significant public health concerns. The rising prevalence of AREDs underscores the urgent need for effective prevention and treatment strategies. This study aimed to explore the causal relationships between circulating micronutrients (CMs) and AREDs.</p><p><strong>Methods: </strong>A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using genetic variants as instrumental variables to assess the effects of fifteen CMs (vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, folate, carotene, copper, calcium, iron, magnesium, potassium, selenium, zinc) on AREDs. Data were sourced from large-scale genome-wide association studies (GWAS). The primary analytical method employed was inverse-variance weighted (IVW), supplemented by sensitivity analyses to confirm the robustness of the results.</p><p><strong>Results: </strong>The MR analysis revealed significant protective effects of selenium against SC (OR = 0.961, 95% CI = 0.932-0.991, P = 0.012) and DR (OR = 0.927, 95% CI = 0.870-0.987, P = 0.019). Furthermore, higher genetically predicted magnesium levels were associated with a reduced risk of AMD (OR = 0.679, 95% CI = 0.515-0.895, P = 0.006). However, no significant causal relationships were observed between the other CMs and glaucoma or other AREDs.</p><p><strong>Conclusions: </strong>These findings provided valuable insights into the complex interplay between CMs and AREDs, offering potential pathways for developing targeted nutritional interventions and public health strategies to mitigate the risk of these debilitating conditions.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the future of nutrigenomics: dietitians' perceptions on integration in Indian practice.","authors":"Naomi Angelo Dias Do Rosario, Devaki Gokhale, Manisha Gore","doi":"10.1186/s12263-024-00760-7","DOIUrl":"10.1186/s12263-024-00760-7","url":null,"abstract":"<p><strong>Background: </strong>Nutrigenomics, the study of nutrient-gene interactions, holds immense potential for alleviating India's overburdened healthcare system and improving overall health-related quality of life. Yet, its utility remains in the nascent stages. To understand the factors affecting the implementation of nutrigenomics, we investigate the perceptions of practising dietetic professionals.</p><p><strong>Objective: </strong>The purpose of this study was to investigate the perceptions of Indian dietetic professionals related to the implementation of Nutrigenomics and to understand the factors affecting it.</p><p><strong>Methods: </strong>A total of 249 Indian dietetic professionals participated in an online survey between April 2024 - May 2024. This data was then statistically analyzed using the Chi-square test and Fisher's Exact test. Furthermore, in-depth interviews were conducted for 10 out of the 249 participants, the data collected from the interviews were analysed using reflexive thematic analysis.</p><p><strong>Results: </strong>Majority of the dietetic professionals had high awareness (97.2%) and interest (87.5%) in incorporating genetic testing into their practice. While the survey identified several barriers to its integration, such as high costs, (p-value = 0.000), lack of clinical trials (p-value = 0.013), and ethical concerns (p-value = 0.023). The in-depth interviews highlighted the need for increased education, standardization of testing panels, and collaboration among healthcare professionals to enhance the feasibility of nutrigenomics integration.</p><p><strong>Conclusion: </strong>Indian dietetic professionals express a positive outlook on integrating nutrigenomics into mainstream healthcare practice. However, successful establishment of personalized nutrition in India also requires addressing key challenges with respect to education, cost, training, development of regulatory frameworks and raising public awareness.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"7"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Nigella sativa silver nanocomposite as an alternative therapy against thioacetamide nephrotoxicity.","authors":"Fatma M El-Demerdash, Ansam B Al Mhanna, Raghda A El-Sayed, Tarek M Mohamed, Maha M Salem","doi":"10.1186/s12263-025-00766-9","DOIUrl":"10.1186/s12263-025-00766-9","url":null,"abstract":"<p><p>Nigella sativa (N. sativa) L. (Ranunculaceae), commonly referred to as black cumin, has a long history of usage as an herbal remedy. It has been utilized conventionally and in clinical settings to treat various illnesses. Six groups of male Wister rats were randomly selected as Gp I, represented as control; Gp II administered N. sativa aqueous extract (NSAE); 200 mg/kg/d, Gp III received N. sativa silver nanocomposite (NS-Ag-NC); 0.25 mg/kg/d; Gp IV administered thioacetamide (TAA);100 mg/kg; thrice weekly and Gps V and VI administered NSAE and NS-Ag-NC with TAA for six weeks, respectively. Findings showed that GC-MS analysis of NSAE has a high concentration of phytochemicals with strong antioxidant activity. Results revealed that TAA administration elevated TBARS, H₂O₂, PCC, NO levels, kidney function parameters, LDH activity, and up-regulated TNF-α, IL-1β, NF-kβ, and COX-2 gene expressions. In contrast, enzymatic and non-enzymatic antioxidants and ALP activity were extensively diminished. Also, severe abnormalities in lipid profile, hematological parameters, and histopathological features were noted. On the other hand, the administration of NSAE or NS-Ag-NC followed by TAA intoxication reduces renal impairment, restores the antioxidant system, and downregulates the expression of TNF-α, IL-1β, NF-kβ, and COX-2 genes in rats' renal tissues. Collectively, NS-Ag-NC has more prevalent nephroprotective impacts than NSAE and can adjust the oxidant/antioxidant pathways besides their anti-inflammatory efficacy against TAA toxicity.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"6"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of FHIT gene variant and salty food preference with the incidence of metabolic syndrome.","authors":"Jihyun Kim, Suyeon Lee, Shiva Raj Acharya, Dayeon Shin","doi":"10.1186/s12263-025-00762-z","DOIUrl":"10.1186/s12263-025-00762-z","url":null,"abstract":"<p><strong>Background: </strong>Taste perception plays a critical role in determining dietary choices and adherence to specific dietary patterns, which may lead to metabolic syndrome (MetS). The fragile histidine triad diadenosine triphosphatase (FHIT) gene plays a key role in cellular processes such as apoptosis and DNA repair, and thus may be an important factor in metabolic regulation. Despite this, the relationship between preference for salty foods, FHIT variants, and MetS is still largely unexplored. This study aimed to investigate the interaction between salty food preference and FHIT variation on the risk of MetS in middle-aged Korean adults.</p><p><strong>Results: </strong>Over a mean follow-up of 10.6 years, 796 MetS cases were recorded. With regard to MetS incidence, the interaction between the FHIT rs2006807 variant and salty food preference was shown in women. Notably, women with the CA/CC genotype who preferred salty foods had a 1.42-fold higher incidence of MetS compared to those with the AA genotype who disliked salty foods (hazard ratio 1.42, 95% confidence interval 1.03-1.97).</p><p><strong>Conclusions: </strong>This study highlights the potential impact of genetic factors and taste preferences when combined on the risk of MetS. Specifically, our findings suggest a significant genetic association between the FHIT rs2006807 variant and preference for salty foods, indicating that genetic predisposition may influence dietary choices. These results imply that personalized nutritional strategies that consider both genetic variations and individual dietary preferences may be effective in preventing MetS.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"5"},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial.","authors":"Chao-Qiang Lai, Julie E Gervis, Laurence D Parnell, Alice H Lichtenstein, Jose M Ordovas","doi":"10.1186/s12263-025-00763-y","DOIUrl":"10.1186/s12263-025-00763-y","url":null,"abstract":"<p><strong>Background: </strong>The TCF7L2 gene is a significant genetic factor contributing to the risk of metabolic and cardiovascular diseases (CVD). We previously found that subjects with the TT genotype of TCF7L2 rs7903146 variant, who consume a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype. Yet this association was abolished in subjects with the TT genotype who consumed a Mediterranean-type diet (MetD). However, the mechanism by which MetD diet modulates the association between TCF7L2 and CVD risk is unclear. This study aims to validate these findings under real-world conditions and clinical practice to elucidate the biological mechanisms involved in this correlation.</p><p><strong>Methods: </strong>Thirty-five participants with BMI ranging from 27 to 34 kg/m² were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomly assigned to two dietary intervention groups, ensuring an equal distribution of CC and TT carriers. Each participant followed one of two diets (LF or MetD) for one week, followed by a 10-day washout period before switching to the other diet for one week. Blood samples were collected before and after each diet for metabolomic analysis using nuclear magnetic resonance (NMR) spectroscopy. The differential effect of the diets on triglyceride-rich lipoproteins was determined based on TCF7L2 genotype.</p><p><strong>Results: </strong>The MetD significantly reduced triglyceride-rich lipoprotein concentrations compared to the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD risk compared to CC carriers. However, this difference in risk was not observed with the MetD. Furthermore, the order in which the two diets were crossed affected the triglyceride-rich lipoprotein profile, with LF-MetD regimen showing a stronger effect on triglyceride-rich lipoproteins (TRL) levels than the MetD-LF regimen.</p><p><strong>Conclusions: </strong>Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceride-rich lipoprotein profile, which may reduce their risk of CVD. These results support the notion that genotype is a factor in determining the extent to which the MetD affects cardiovascular health.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decomposed interaction testing improves detection of genetic modifiers of the relationship of dietary omega-3 fatty acid intake and its plasma biomarkers with hsCRP in the UK Biobank.","authors":"Kenneth E Westerman, Chirag J Patel, James B Meigs, Daniel I Chasman, Alisa K Manning","doi":"10.1186/s12263-025-00765-w","DOIUrl":"10.1186/s12263-025-00765-w","url":null,"abstract":"<p><p>Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP). We considered an approach that decomposes the overall genetic effect modification into components upstream and downstream of a molecular mediator to increase the potential to discover gene-N3FA interactions. Simulations demonstrated improved power of the upstream and downstream tests compared to the standard approach when the molecular mediator for many biologically plausible scenarios. The approach was applied in the UK Biobank (N = 188,700) with regression models that used measures of dN3FA (based on fish and fish oil intake), pN3FA (% of total fatty acids measured by nuclear magnetic resonance), and hsCRP. Mediation analysis showed that pN3FA fully mediated the dN3FA-hsCRP main effect relationship. Next, we separately tested modification of the dN3FA-hsCRP (\"standard\"), dN3FA-pN3FA (\"upstream\"), and pN3FA-hsCRP (\"downstream\") associations. The known FADS1-3 locus variant rs174535 reached p = 1.6 × 10^-12 in the upstream discovery analysis, with no signal in the downstream analysis (p = 0.94). It would not have been prioritized based on a naïve analysis with dN3FA exposure and hsCRP outcome (p = 0.097), indicating the value of the decomposition approach. Gene-level enrichment testing of the genome-wide results further prioritized two genes from the downstream analysis, CBLL1 and MICA, with links to immune cell counts and function. In summary, a molecular mediator-focused interaction testing approach enhanced statistical power to identify GxEs while homing in on relevant sub-components of the dN3FA-hsCRP pathway.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in some colorectal cancer cell lines.","authors":"Esmaeel Babaeenezhad, Peyman Khosravi, Mostafa Moradi Sarabi","doi":"10.1186/s12263-025-00764-x","DOIUrl":"10.1186/s12263-025-00764-x","url":null,"abstract":"<p><strong>Background: </strong>Promoter methylation silencing of peroxisome proliferator-activated receptor gamma (PPARγ) and dysregulation of the PPARγ/COX2 axis contribute to colorectal cancer (CRC) pathogenesis. This study investigated for the first time the effects of dietary polyunsaturated fatty acids (PUFAs) on promoter methylation of PPARγ and the PPARγ/COX2 axis in five CRC cell lines.</p><p><strong>Methods: </strong>Five CRC cell lines (SW742, HCT116, Caco2, LS180, and HT29/219) were treated with 100 µM of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or linoleic acid (LA). The methylation patterns of the four regions within the PPARγ promoter were determined using methylation-specific PCR (MSP). Additionally, the mRNA expression levels of PPARγ and COX2 were examined using RT-qPCR.</p><p><strong>Results: </strong>Our results showed that M3 segment within the PPARγ promoter was hemimethylated in SW742 cells, whereas other cell lines remained unmethylated in this region. The M4 region was hemimethylated in all the CRC cell lines. Of all PUFAs, DHA demethylated the M3 region of the PPARγ promoter in SW742 cells and the M4 region in Caco2 cells. Functionally, these changes were accompanied by significant upregulation of PPARγ in SW742 (9.22-fold; p = 0.01) and Caco2 cells (8.87-fold; p = 0.04). Additionally, COX2 expression was significantly downregulated in all CRC cell lines after exposure to PUFAs (p < 0.05).</p><p><strong>Conclusions: </strong>This study demonstrated that PUFAs, particularly DHA, altered PPARγ promoter methylation and expression, as well as modulated the PPARγ/COX2 axis in CRC cells in a cell type-dependent manner. DHA was more effective than the other PUFAs in regulating PPARγ promoter methylation. Our results highlight the potential clinical use of PUFAs in CRC treatment.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"2"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of single nucleotide polymorphisms (SNPs) in antioxidant-enzyme genes on the concentrations of folate, homocysteine and glutathione in plasma from healthy subjects after folic acid supplementation - a randomized controlled crossover trial.","authors":"Mohammad Azam Mansoor, Tonje Holte Stea, Audun Slettan, Erandie Perera, Ridmi Maddumage, Darshana Kottahachchi, Dhikra Saleem Ali, Rona Cabo, Rune Blomhoff","doi":"10.1186/s12263-024-00761-6","DOIUrl":"10.1186/s12263-024-00761-6","url":null,"abstract":"<p><strong>Background: </strong>One-carbon metabolism links folate and methionine metabolism and this is essential for nucleotide synthesis in the cells. Alterations in one-carbon metabolism are associated with cardiovascular disease (CVD), type 2 diabetes and cancer. Our aim was to investigate whether SNPs in antioxidant-enzyme genes impact the concentrations of folate in serum (s-folate), plasma total homocysteine (p-tHcy) and total glutathione in plasma (p-tGSH) in healthy subjects after supplementation with folic acid.</p><p><strong>Methods: </strong>In a randomized, double blind, crossover study, healthy subjects received 0.8 mg folic acid per day or a placebo for two weeks. Twenty-four male, and sixty-seven female subjects participated in this study. Participants were aged 36.4 ± 14.8 years (mean ± SD). We studied SNPs in six genes by PCR methods. The concentrations of s-folate, p-tHcy and p-tGSH were measured in fasting samples with Cobas and an HPLC-fluorescence method. Student T-tests and ANOVA were used for the statistical calculations.</p><p><strong>Main findings: </strong>The subjects with SNP (rs4880) in superoxide dismutase (SOD2) gene (CC) allele had higher concentrations of s-folate and lower concentrations of p-tHcy than subjects with (CT + TT) alleles, (p = 0.014 and p = 0.012). Contrary to SOD2 (CC) allele, the subjects with SNP (rs1001179) catalase (CAT) CC allele had lower concentrations of s-folate (p = 0.029), higher concentrations of p-tGSH (0.017) and higher concentrations of p-tHcy before and after folic acid supplementations (p = 0.015, p = 0.017) than the subjects with (CT + TT) allele. Glutathione transferase (theta)1 (GST-T1) genotype was associated with higher concentrations of s-folate than GST-T0 before (p = 0.025) and after folic acid supplementation (p = 0.047). SNP (rs1050450) in glutathione peroxidase (GPX1) had also impact on the concentrations of p-tGSH (p = 0.011) in healthy subjects.</p><p><strong>Conclusion: </strong>SNPs in SOD2 (rs4880), CAT (rs1001179), and GST1 impact the concentrations of s-folate, and p-tHcy in healthy subjects before and after folic acid supplementation. Our findings suggest that SNPs in antioxidant-genes have a role in health and disease by impacting the concentrations of s-folate, p-tHcy and p-tGSH.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"20 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A double knockout for zinc transporter 8 and somatostatin in mice reveals their distinct roles in regulation of insulin secretion and obesity.","authors":"Zhongyue Yang, Catherine P Kirschke, Yimeng Cai, Liping Huang","doi":"10.1186/s12263-024-00759-0","DOIUrl":"10.1186/s12263-024-00759-0","url":null,"abstract":"<p><strong>Background: </strong>Both zinc transporter 8 (ZnT8) and somatostatin (Sst) play crucial roles in the regulation of insulin and glucagon secretion. However, the interaction between them in controlling glucose metabolism was not well understood. The aim of this study was to explore the interactive effects of a double knockout of Znt8 and Sst on insulin and glucose metabolism in mice.</p><p><strong>Methods: </strong>Co-expression of ZnT8 with hormones secreted from gastrointestinal endocrine cells of mice was determined using immunofluorescence. Male Znt8 knockout (Znt8KO), Sst knockout (SstKO), double knockout for Sst and Znt8 (DKO), and the wild-type (WT) mice were fed a regular chow diet (CD) or a high-fat diet (HFD) at 3 weeks old for 15 weeks. Weights and fasting or fed glucose levels were determined. Glucose and insulin tolerance tests were performed; metabolic-relevant hormone levels including insulin, glucagon, glucagon-like peptide 1, Pyy, and leptin were determined.</p><p><strong>Results: </strong>ZnT8 is co-expressed with Sst in a subpopulation of endocrine D cells in the gastrointestinal tract. The absence of ZnT8 expression resulted in an increased density of the dense cores in the secretory granules of the D cell. DKO mice had reduced weight compared to WT when maintained on the CD. Compared to Znt8KO and SstKO, DKO mice did not show significant differences in fed or fasting blood glucose level regardless of dietary conditions. However, the CD-fed DKO mice had impaired insulin secretion without alterations in islet morphology or numbers. Moreover, DKO mice displayed diet-induced insulin resistance and disrupted secretion of metabolic-related hormones.</p><p><strong>Conclusions: </strong>Somatostatin as well as a normal insulin sensitivity are required for normalizing glucose metabolism in Znt8KO mice. ZnT8 may play a role in regulating fat mass and leptin secretion. These findings shed light on the multifaceted nature of Znt8 and Sst interactions, opening new avenues to understand their roles in controlling glucose metabolism and fat mass.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"24"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein inhibited endocytosis and fibrogenesis in keloid via CTGF signaling pathways.","authors":"Chun-Te Lu, Jiunn-Liang Ko, Chu-Chyn Ou, Chih-Ting Hsu, Yu-Ping Hsiao, Sheau-Chung Tang","doi":"10.1186/s12263-024-00758-1","DOIUrl":"10.1186/s12263-024-00758-1","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate soy isoflavones' effect and potential use-specifically genistein-in treating human keloid fibroblast cells (KFs) and in a keloid tissue culture model.</p><p><strong>Methods: </strong>To investigate the effects of genistein on keloid, a wound-healing assay was performed to detect cell migration. Flow cytometry was used to measure apoptosis. Western blotting and immunofluorescence staining were performed to detect the expression of target proteins. KF tissues were isolated, cultured, and divided into the control, silenced connective tissue growth factor (CTGF) proteins, and shNC (negative control) groups.</p><p><strong>Results: </strong>Genistein suppressed cell proliferation and migration, triggering the cell cycle at the G2/M phase and increasing the expression of p53 dose-dependent in keloids. Genistein inhibited the expression of COL1A1, FN, and CTGF mRNA and protein. Knockdown CTGF reduced the migrated ability in KFs. Genistein also abated TGF-β1-induced keloid fibrosis through the endocytosis model. Separated and cultured the keloid patient's tissues decreased the cell migration ability by genistein treatment and was time-dose dependent.</p><p><strong>Conclusions: </strong>This study indicated that genistein-induced p53 undergoes cell cycle arrest via the CTGF pathway-inhibited keloid cultured cells, and genistein suppressed the primary keloid cell migration, suggesting that our research provides a new strategy for developing drugs for treating keloids.</p>","PeriodicalId":55123,"journal":{"name":"Genes and Nutrition","volume":"19 1","pages":"23"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}